In osteoarthritis the integrity of articular cartilage is damaged, compromising the mechanical functioning, and the self-repair capability of the tissue. Both of these tissue functions derive from the properties of the macromolecules comprising the extensive extracellular matrix of adult articular cartilage. The goal of this project is to elucidate the roles of collagen and proteoglycan, the principal matrix macromolecules, in the biomechanical and homeostatic functioning of normal and osteoarthritic cartilage. It aims to determine the molecular packing of collagen fibrils in normal and osteoarthritic cartilages from human femurs as a function of age, and to examine the relationship between the fibrillar structure and proteoglycan composition; to determine the pathways for the transport of cell nutrients and matrix precursors throughout articular cartilage in terms of the space filling structures of collagen and proteoglycan; and to determine the mechanisms by which collagen fibrils are deformed by osmotic and mechanical forces, with the view of characterizing at the molecular level the biomechanics of cartilage, and the factors regulating the self repair capabilities of cartilage cells. The research program will consist of x-ray diffraction studies of cartilages while in different physiological states in conjunction with a variety of biochemical and physiocochemical protocols.